The major goal of the proposed research is to understand how growth is controlled in livestock animals. Three hormones known to be involved in growth control are growth hormone (GH), growth hormone releasing factor (GRF), and insulin-like growth factor I (IGF-I). During the past three years it has become possible to introduce new genes into large animals and thus to study the effect of the products of these genes on the animal. These animals are called transgenic. The three specific aims of the proposed research are: Specific Aim 1: To achieve high level expression of GH, GRF and IGF-I transgenes in sheep, pigs and cows. Specific Aim 2: To study the effects of these transgenes on growth and development of each species. Specific Aim 3: To develop gene constructs with a higher level of expression and better transcriptional control through pilot studies in mice and rabbits and subsequent testing in larger animals. Several lines of animals in each of the three large animal species will be produced that express each of the three growth-related genes. Fusion genes in which heterologous promoter/regulators are connected to the growth genes will be used to achieve and control expression of the individual genes. This will create lines of animals in which the blood levels of the hormones resulting from the new genes are elevated and ideally may be regulated by external experimental factors. These animals will provide unique models to understand how each of these hormones influences the growth and physiology of animals in each species. The proposed studies have considerable relevance to major biological questions, and the results will benefit livestock producers. The ability to control the growth of large animals would be of enormous value to the farm economy.